免疫系统疾病(1).ppt

,单击此处编辑母版标题样式,*,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Diseases of Immunity,（,免疫性疾病）,刘 颖,Office,：,Rm.214,East No.1 Building,E-mail:,Overview,Immune system:,A Two-edged sword,:,responsible for defending us against the countless pathogenic microbes or tumors,hypersensitive or abnormal reaction is the cause of some diseases,Hypersensitivity diseases have been grouped into four major categories based upon their underlying causes.,The Common Types of the Diseases of Immunity,1,.Transplant Rejection,2,.Hyperactive immunity,：,Diseases of Autoimmunity,systemic lupus erythematosus(SLE),3,.Immunodeficiency:,Immunodeficiency syndrom,acquired,Immunodeficiency syndrom(AIDS),Transplant Rejection,Host anti-donor allograft,(,宿主抗移植物反应,),2.Donor allograft anti-Host,(,移植物抗宿主反应,),Cell mediated hypersensitivity,Antibody mediated hypersensitivity,Mechanisms of Graft Rejection,Rejection of allografts is a response to Major Histocompatibility Complex(MHC,抗原,),also referred as to Human Leukocyte antigen（HLA,抗原）,Both T cells and antibodies reactive with the graft are involved in the rejection of most solid-organ allografts,T-Cell-Mediated Rejection:,cytotoxic lymphocyte(CTLs,CD8+T),CD4+T,macrophages,Antibody-Mediated Rejection:,Direct pathway:Alloantibodies directed against graft MHC molecules,Indirect pathway:other alloantigens bind to the graft endothelium and cause injury(and secondary thrombosis)via complement activation and recruitment of leukocytes.,Mechanisms of Graft Rejection,Classification,1.,Hyperacute Rejection,Occurs within minutes to a few hours after transplantation,2.,Acute Rejection,Occurs within days,weeks,months even years.,3.,Chronic Rejection,Occurs in months to years,Hyperacute Rejection,Mechanisms,Antidonor antibodies(MHC or ABO antigens)are present in the circulation of the host before transplant.,In any event,transplantation in this setting results in immediate rejection because the circulating antibodies rapidly bind to the endothelium of the grafted organ,with subsequent complement fixation and vascular thrombosis.,Gross:,Cyanotic,mottled,flabby and soft,swollen,Widespread hemorrhagic cortical necrosis,May excrete only a few drops of bloody fluid,MORPHOLOGY,LM:,(1)Widespread acute arteritis and arteriolitis:,Fibrinoid necrosis of walls,Thrombosis,(2)Ischemic necrosis,Acute Rejection,It is the most common type of transplant rejection in a nonimmunosuppressed host or may appear months or even years later in the presence of adequate immunosuppression,It is mainly conducted by,cellular rejection,in the early stage.However,humoral(,体液,)rejection,also participate in the later stage.,1.,Acute cellular rejection,:,most commonly seen within the first months after transplantation,extensive interstitial CD4+and CD8+T-cell infiltration with edema and mild interstitial hemorrhage,2.,Acute humoral rejection-,-antibody-mediated rejection:also called as blood vessel type rejection.,necrotizing vasculitis with endothelial cell necrosis;neutrophilic infiltration;deposition of antibody,complement,and fibrin;and thrombosis,Acute Rejection,Histologically,cellular rejection,is marked by an interstitial mononuclear cell infiltrate with associated edema and parenchymal injury,humoral rejection,is associated with vasculitis.,Acute cellular rejection,T-cell infiltration with edema and mild interstitial hemorrhage,Blood vessel type rejection,necrotizing vasculitis,Chronic Rejection,It is usually the result from acute rejection,and not respond to standard immunosuppression therapy.,Gross:shrunk kidney.,Microscope:dominated by vascular changes(smooth muscle cell proliferation and extracellular matrix synthesis),interstitial fibrosis,and loss of renal parenchyma,血管闭塞性动脉内膜炎,Diseases of Autoimmunity,Tolerance(unresponsiveness)to self-antigens is a fundamental property of the immune system,breakdown is the basis of autoimmune diseases,Systemic Lupus Erythematosus(SLE),Characteristics:,1.,Predominantly in young women.,2.,Mainly conducted by humoral immunity.,3.,Multiple organs damage,multisystem autoimmune disease,4.Variant clinical manifestation:Acute or insidious onset that may involve virtually any organ in the body,affects principally the skin,kidneys,serosal membranes,joints,and heart,5.A fairly common disease,a strong(approximately 9:1)female preponderance,affecting 1 in 700 women of childbearing age.,Etiology and Pathogenesis,The fundamental defect in SLE is a failure to maintain self-tolerance.,A large number of autoantibodies is produced that can damage tissues either directly or in the form of immune complex deposits,Antibodies include:,1.Antinuclear Antibodies,(1)antibodies to DNA,(2)antibodies to histones,(3)antibodies to nonhistone proteins bound to RNA,(4)antibodies to nucleolar antigens,2.Other Autoantibodies,Antibodies against blood cells,Antiphospholipid antibodies,Etiology and Pathogenesis,1.,Genetic Factors,(1)There is a high rate of concordance(25%)in monozygotic twins versus dizygotic twins(1%to 3%).,(2)Family members have an increased risk of developing SLE.And up to 20%of clinically unaffected first-degree relatives may reveal autoantibodies.,(3)Positive association between SLE and polymorphism of HLA-DQ locus.,Etiology and Pathogenesis,2.,Nongenetic Factors,(1)Most patients treated with procainamide,(,普鲁卡因胺,),for more than 6 months develop ANAs,(,抗核抗体）,and 20%appear SLE.,(2)Sex hormones,especially estrogens.,(3)Exposure to ultraviolet light.,3.,Immunologic Factors,Intrinsic B-cell hyperactivity was considered a central feature of SLE pathogenesis.,Mostly type III hypersensitivity reaction,Morphology,LE body,:ANAs attack the damaged cells nuclear,the cell lost its chromatin pattern,and become homogeneous,to produce so-called LE body(hematoxylin body).The neutrophil or macrophage that has engulfed the LE body is referred as to,LE cell,2.The Basic Morphologic Changes:,(1)Acute stage:acute necrotizing vasculitis,Fibrinoid,necrosis of blood vessel wall,(2)Chronic stage:perivascular fibrosis,producing Onion-skin lesions,Involved Organs,Kidney:,Kidney involvement is one of the most important clinical features of SLE.Renal failure being the most common cause of death.,SLE,glomerolonephritis,:,occur in about 60%SLE patients.The typical lesions are fibrinoid necrosis,wire loop and so on.If detected by immuno-fluorescence and electron microscope,almost all cases show some renal abnormality.,World Health Organization,（,WHO,）,morphologic classification,5 patterns of glomerular disease in SLE(none of which is specific to the disease):,class I,normal by light,electron,and immunofluorescence microscopy(less than 5%of SLE patients);,class II,mesangial lupus glomerulonephritis;,class III,focal proliferative glomerulonephritis;,class IV,diffuse proliferative glomerulonephritis;,class V,membranous glomerulonephritis.,wire loop,Immunofluorescence“,满堂亮”,2.,Skin,:,Involved in a vast majority of patients.,A characteristic erythematous are butterfly pattern in about half.,Histologically,there is liquefactive degeneration of the basal layer of the epidermis,edema at the dermoepidermal junction,and mononuclear infiltrates around vessels and skin appendages.,Immunofluorescence microscopy reveals deposition of Ig and complement at the dermoepidermal junction,Involved Organs,liquefactive degeneration of the basal layer of the epidermis and edema at the dermoepidermal junction,immunofluorescence stained for IgG reveals deposits of Ig along the dermoepidermal junction.,3.,Heart:,Nonbacterial verrucous endocarditis;pericarditis;and myocarditis.,Involved Organs,1-to 4-mm warty deposits,Myocarditis in the form of a nonspecific mononuclear cell infiltrate,and valvular lesions,Pericardium and pleura,in particular,are serosal membranes that show a variety of inflammatory changes,4.,Others:,more than 90%patients have,joint involvement,:nonspecific mononuclear cell infiltration in the synovial membranes.Erosion of the membranes and destruction of articular cartilage,CNS,involvement is also very common:vascular lesions causing ischemia or multifocal cerebral microinfarcts,spleen,may be moderately enlarged,central arteries characteristically show thickening and perivascular fibrosis,producing onion-skin lesions.,lung,may reveal interstitial fibrosis,along with pleural inflammation;,liver,shows nonspecific inflammation of the portal tracts.,Involved Organs,Clinical and pathological correlations,The manifestations are extremely,variable,because of multiple organs damaged.,The,diagnosis of SLE is obvious,in a young woman with a classic butterfly rash over the face,fever,arthritis,pleuritic chest pain,and photosensitivity,（光敏）,ANAs,can be found in virtually 100%of patients;,anti-dsDNA,antibodies and,antibodies to,Smith(Sm)antigen,are considered highly diagnostic of SLE.,Serum complement,levels are low,90%five-year and 80%ten-year,survivals,Renal failure,intercurrent,（伴发的）,infections,and diffuse CNS involvement are,major causes of death,.,Acquired Immuno-Dificiency Syndrom(AIDS),Concept:,AIDS is a retroviral disease caused by the,human immunodeficiency virus,(HIV).,It is characterized by infection and depletion of CD4+T lymphocytes,and by profound immunosuppression leading to opportunistic infections,secondary neoplasms,and neurologic manifestations,Originated from Africa,but first described in the United States in 1981,1985,年，一位到中国旅游的外籍人士患病入住北京协和医院后很快死亡，后被证实死于艾滋病。这是我国第一次发现艾滋病病例。,more than 22 million people have died of AIDS;about 42 million people are living with the disease;estimated 5 million infections each year;,95%of HIV infections are in developing countries,Africa alone carrying more than 50%of the HIV burden,AIDS represents the fifth most common cause of death in adults between the ages of 25 and 44,Epidemiology of AIDS,Five groups at risk for developing AIDS:,1.Homosexual or bisexual males,2.Intravenous drug abusers,3.Recipients of blood and blood components,4.Hemophiliacs,（血友病患者）,5.Heterosexual contacts of members of other high-risk group,6.about 10%of cases the risk factors are unknown or not reported,Three Major Transmission Routes,1.,Sexual transmission:accounting for more than 75%cases in the world.,2.Parenteral,（注射）,transmission:Including three groups,(1)intravenous drug abusers,(2)hemophiliacs receiving factor,or,(3)random recipients of blood transfusion,3.Mother-to-infant transmission:vertical transmission rate worldwide vary from 25%to 30%.,Etiology of AIDS,HIV has two genetically different but antigenically related forms.,HIV-1 is the more common type associated with AIDS in the United States,Europe,and Central Africa,HIV-2 causes a similar disease principally in West Africa,Retroviruse HIV-1 virion is spherical and contains an electron-dense,cone,（圆锥）,-shaped core surrounded by a lipid envelope derived from the host cell membrane,Pathogenesis of AIDS,The two major targets of HIV infection are the,immune system,and the,CNS,Life Cycle of HIV:,The CD4 molecule is a high-affinity receptor for HIV infection.,The virus bind and entry the cells.Then produce new virus in the CD,4,+,cells.The infected cells were killed,and the virus will infect other CD,4,+,cells.,The loss of CD,4,+,cells.The cytokines production reduced so that the whole immuno-system break-down.,Progression of HIV Infection:,acute infection of mucosal T cells and DCs;,viremia with dissemination of virus;,latent infection of cells in lymphoid tissue;,continuing viral replication and progressive loss of CD4+T cells,Mechanisms of T-cell Depletion in HIV Infection,Three phase,(1),an early acute phase,(2)a middle chronic phase,(3)a final crisis phase,Natural History of HIV Infection,In the absence of treatment,most patients with HIV infection develop AIDS after a chronic phase lasting 7 to 10 years,Morphology of AIDS,The clinical manifestations of HIV infection range from a mild acute illness to severe disease,In USA typical adult patients presents:,fever,weight loss,diarrhea,generalized lymphadenopathy,multiple opportunistic infections,neurologic disease,secondary neoplasms,Morphology of AIDS,1.,Lymphoid Tissue,In early stages:a marked follicular hyperplasia;medulla,（髓质）,contains abundant plasma cells,With disease progression:severe follicular involution,（退化）,and generalized lymphocyte depletion,In advanced stage,：,all kinds of lymphocytes decreased.burnt-out lymph nodes are atrophic and small and may harbor numerous opportunistic pathogens,Morphology of AIDS,2.,Opportunity infection,Opportunistic infections have accounted for approximately 80%of deaths in patients with AIDS,Pneumocystis,（肺胞子虫）；,CMV,；,herpes simplex,；,M.tuberculosis,（鸟型）；,Cryptococcal,（隐球菌）,meningitis,；,Cryptosporidium,（隐孢子虫）,霉菌 传染性软疣,fungus,卡氏肺孢子虫,Opportunity infection of lung,CMV,fungus,herpes simplex,Cryptococcus,弓形虫,Cryptosporidium,（隐孢子虫）,Morphology of AIDS,3.,Secondary malignant tumors,Kaposi sarcoma:the most common neoplasm,non-Hodgkin lymphomas:the second common,cervical cancer in women,Kaposi sarcoma in mouth,spindle cells(similar to endothelial cells and smooth muscle cells)vascular channels with red cells,hemosiderin or hemorrhage inside,Thank you!,